Sexually transmitted infections (STIs) are strongly associated with HIV risk. However, population based studies to manage STIs as a way of reducing HIV risk have had limited success. Recent studies show that elevated genital tract inflammatory cytokines are strongly associated with an increased risk of HIV acquisition, and STIs are one of the commonest causes of elevated genital tract cytokines. This interest in the role of cytokines in HIV acquisition has reinvigorated interest in STIs and whether better management strategies can have a role in HIV risk reduction. HIV and STIs extremely common in the South African province of KwaZulu-Natal (KZN) where there are many challenges with STI diagnosis and treatment, including the reliance on syndromic management, an approach based on the recognition of STI syndromes (vaginal discharge, urethral discharge and genital ulceration), followed by treatment targeting the common causes of the syndrome. This approach has a low sensitivity and specificity for detecting STIs, leaving 80-85% undiagnosed and untreated. Other challenges with current STI management include limited partner notification and treatment. At a population level, the result is that most STIs remain untreated and the burden of STIs within the community remains unchecked. Our goal is to determine if an innovative, enhanced program of STI management will result in a higher cure rate and a lower recurrence rate, with a subsequent reduction in genital inflammatory cytokines and hence HIV risk. This proof of concept study will be addressed by identifying individuals with STIs using an innovative, point-of-care diagnostic test (an automated, cartridge-based nucleic amplification assay (GeneXpert) for the simultaneous detection of N. gonorrhoeae and C. trachomatis. This technology has recently been introduced on a large scale across South Africa to detect tuberculosis (TB) and TB drug resistance, thereby accelerating diagnosis, treatment and enhancing public health initiatives to control TB. We will then measure 48 genital tract cytokines using Bio-Plex Pro Human Cytokine kits and a Bio-Plex MagPix Array Reader. We will then treat them immediately with appropriate therapy under direct supervision, giving the participants the same treatment to take home for their sexual partners (expedited partner therapy) and asking them to return after 6 weeks and 3 months for a test of cure. We will then test participants for genital tract inflammatory cytokines and determine if these have decreased. Overall, our innovative enhanced management package for STI care, offers the best opportunity to reduce STIs, by ensuring that the individual is cured and reducing the risk of reinfection using expedited partner therapy. This will allow us to determine whether genital inflammation can be reduced after effective STI treatment, and ultimately reduce the risk of HIV acquisition in SA and also in the USA.